Natural acylcyclopentenediones comprise only a few compounds with limited occurrence. Regarding the biological activity of this unique class of compounds, methyllinderone was cytotoxic against several cancer cell lines, while methyllucidone showed moderately antifungal activity against wheat leaf rust caused by Puccinia recondite. A significant work in this regard was the identification of the synthetic analog 2-(1-methoxy-3-phenyl-2-propenylidene)-cyclopent-4-ene-1,3-dione as a potent inhibitor of human chymase, a potential drug target associated with cardiovascular diseases and chronic inflammation following fibrosis. The synthesis of this compound was inspired by the natural product methyllinderone, a moderate inhibitor of the enzyme identified from the screening of a compound library. It is noted, however, that the cyclopent-4-ene- and cyclopentane-1,3-dione structural moieties are present in a number of synthetic compounds with therapeutic applications or potential.
The present inventors have discovered that the ethanol extract of the whole Peruvian plant, Piper coruscans H.B. & K. exhibits significant antifungal activity against Candida albicans (IC50<2 μg/mL). A subsequent antifungal bioassay-guided fractionation of this extract led to identification of novel antifungal cyclopentenedione derivatives of the present invention.